Search Results (104)

Hematopoietic stem cell transplant (HSCT) is a curative therapy for acute lymphoblastic leukemia (ALL), but its success is limited by chronic graft-versus-host disease (cGvHD) and disease relapse. A central challenge is uncoupling the graft-versus-leukemia (GvL) effect from cGvHD. Early changes in the bone marrow microenvironment following HSCT may offer a predictive window into these divergent outcomes. We conducted a retrospective, single-center, exploratory study on 14 pediatric ALL HSCT patients. Applying single-cell antibody-sequencing (AbSeq) on archived bone marrow aspirates collected 60–100 days post-HSCT, we evaluated immune patterns associated with the development of cGvHD or ALL relapse after day 114. cGvHD after day 114 was associated with upregulation of the endoplasmic reticulum (ER) stress transcription factor XBP1 in transitional B cell and IgM memory B cell populations, a mincle^highPD1⁻ neutrophil population, and exhausted LAG3⁺ effector memory T cells (T_EM). ALL relapse after day 114 was associated with higher CD22, CD24, and ARG1 expression in M(IL-4)-like macrophages and exhausted TIGIT⁺ T_EM. Results from this exploratory study suggest that marrow immune signatures of B cell ER stress preceding later development of cGvHD and macrophage-mediated immune evasion preceding relapse may potentially be early biomarkers for separating GvL from cGvHD in ALL HSCT. Validation with larger cohorts is warranted. Full article

Allogeneic hematopoietic stem cell transplantation (HSCT) is a medical procedure to treat hematologic malignancies and restore bone marrow function. However, this approach may lead to graft-versus-host disease (GvHD), a major cause of mortality and morbidity after allogeneic HSCT. Some studies have suggested the involvement of gut microbiota in the development and prognosis of GvHD. In this context, the main objective of this study was to compare the fecal microbiome composition and short-chain profile of pediatric patients who underwent successful HSCT, developed GvHD or died. The bacterial composition was analyzed using 16S rRNA gene sequencing, while short-chain fatty acids (SCFAs) were quantified by gas chromatography. Fecal samples at engraftment were mainly characterized by a loss of bacterial diversity, a depletion of sequences belonging to the genus Blautia and significantly lower concentrations of fecal butyrate and acetate compared with those obtained before HSCT and 100 days after HSCT. Our findings confirm that children experiencing GvHD after HSCT have distinct gut microbiota and SCFA profiles, which might contribute to developing new microbiota-targeted strategies for GvHD prevention during HSCT procedures. Full article

Background: Myeloid sarcoma (MS) is a malignant extramedullary tumor that occurs in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myeloid leukemia (CML). The standard first-line treatment for MS is intensive chemotherapy according to the AML protocol, regardless of bone marrow involvement. The role of allogeneic hematopoietic stem cell transplantation (alloHSCT) in the treatment of pediatric patients with MS requires further investigation. The aim of the study was to evaluate treatment outcomes for MS in pediatric patients with a focus on assessing the impact of allogeneic hematopoietic stem cell transplantation (alloHSCT) on treatment efficacy. Material and Methods: The study included 64 patients aged 0 to 19 years from 15 pediatric oncology centers in Poland who were diagnosed with MS between 1998 and 2024. An Excel database was created to collect data on clinical features and treatment methods and outcomes. Results: The probability of 5-year overall survival (pOS) for the entire cohort was 0.63 ± 0.07, while the 5-year event-free survival (pEFS) and 5-year relapse-free survival (pRFS) were 0.62 ± 0.07 and 0.72 ± 0.07, respectively. Treatment outcomes were compared between patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) in first complete remission (ICR) (n1 = 17/64; 27%) and those who did not receive alloHSCT (n2 = 47/64; 73%). In the alloHSCT group (n1), the estimated survival probabilities were pOS = 0.49 ± 0.13, pEFS = 0.44 ± 0.14, and pRFS = 0.40 ± 0.14. In the non-alloHSCT group (n2), these values were pOS = 0.68 ± 0.08, pEFS = 0.68 ± 0.08, and pRFS = 0.84 ± 0.06. The difference in pRFS between groups n1 and n2 was statistically significant (p = 0.0049). Extramedullary relapses were more frequently observed in patients who had undergone allogeneic hematopoietic stem cell transplantation (alloHSCT) (p = 0.0001). Conclusions: Allogeneic hematopoietic stem cell transplantation (alloHSCT) does not improve the outcome of patients with MS. Further research is needed to identify effective strategies for sustaining remission in patients with MS after alloHSCT. Full article

Introduction: Intensive chemotherapy protocols and hematopoietic stem cell transplantation (HSCT) in children with cancer frequently lead to severe complications, such as mucositis and immune dysfunction. A growing body of evidence indicates that these complications are closely associated with the patient’s nutritional status and the composition of the gut microbiome, which becomes profoundly destabilized as a result of cytotoxic therapy and antibiotic use. Background: The aim of this review is to critically evaluate the current state of knowledge on the interplay between gut dysbiosis, metabolomic profiles—with particular emphasis on short-chain fatty acids (SCFAs)—and treatment-related toxicity in pediatric patients, as well as to delineate pathways toward personalized nutritional therapy. Methods: A narrative review was conducted, including clinical and preclinical studies published between January 2015 and October 2025. PubMed/MEDLINE, Embase, Cochrane Library, and other databases were searched, focusing on changes in microbiome composition, correlations between gut-derived metabolites and the severity of complications (sepsis, graft-versus-host disease [GvHD], mucositis), and the effects of targeted nutritional interventions (probiotics, prebiotics, postbiotics, and fecal microbiota transplantation [FMT]) on microbiome modulation during anticancer therapy. Results: The analysis demonstrates that pediatric oncologic treatment leads to a marked reduction in microbial diversity, including the loss of protective Clostridiales taxa (e.g., Faecalibacterium), accompanied by an overgrowth of Proteobacteria pathobionts. Metabolomic profiling indicates that low SCFA levels (e.g., butyrate < 20–50 µmol/g) are a strong predictor of severe mucositis, prolonged neutropenia, and an increased risk of sepsis. Interventions aimed at restoring eubiosis and enhancing SCFA production show potential in strengthening the intestinal barrier, modulating immune responses, and enabling maintenance of the planned relative dose intensity (RDI) of chemotherapy by reducing treatment-related toxicity. Conclusions: Gut microbiome profiling and fecal metabolomics represent promising prognostic tools in pediatric oncology. There is an urgent need for further research employing “omics”-based approaches to develop precise, individually tailored nutritional protocols. Such strategies, including postbiotics and FMT, may minimize treatment-related adverse effects and improve long-term clinical outcomes in pediatric patients. Full article

Mesenchymal stem/stromal cells (MSCs) exhibit broad differentiation capability and strong immunoregulatory potential mediated through intercellular communication and the release of diverse paracrine mediators. They represent a promising but still investigational therapeutic approach for managing complications associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). This review provides an updated synthesis of MSC biology, their bidirectional interaction with immune cells, and their functional contribution to the hematopoietic niche. It also evaluates current clinical evidence regarding the therapeutic roles of MSCs and MSC-derived extracellular vesicles (EVs) in acute and chronic graft-versus-host disease (aGVHD/cGVHD), as well as in poor graft function. Mechanistic insights encompass macrophage polarization toward an anti-inflammatory phenotype, inhibition of dendritic cell maturation, enhancement of regulatory T-cell expansion, and modulation of cytokine signaling pathways. Within the bone marrow milieu, MSCs contribute to stromal restoration and angiogenic repair. Recent phase II/III trials in steroid-refractory (SR)-aGVHD have demonstrated overall response rates ranging from 48 to 71%. Efficacy appears particularly enhanced in pediatric patients and with early MSC administration. Across studies, MSC therapy shows a favorable safety profile; however, heterogeneity in response and inconsistent survival outcomes remain notable limitations. For poor graft function, limited prospective studies indicate hematopoietic recovery following third-party MSC infusions, and combination approaches such as co-administration with thrombopoietin receptor agonists are under investigation. MSC-derived EVs emulate many immunomodulatory effects of their parental cells with a potentially safer profile, though clinical validation remains in its infancy. MSC-oriented interventions hold substantial biological and therapeutic promise, offering a favorable safety margin; however, clinical translation is hindered by product variability, suboptimal engraftment and persistence, and inconsistent efficacy across studies. Future directions should emphasize standardized manufacturing and potency assays, biomarker-driven patient and timing selection, optimized conditioning and dosing strategies, and the systematic appraisal of EV-based or genetically modified MSC products through controlled trials. Full article

(1) Background: Cutaneous secondary malignant neoplasms are a growing survivorship burden after pediatric cancers and hematopoietic stem cell transplantation (HSCT), yet skin-focused surveillance remains inconsistently implemented. (2) Objective: To synthesize current molecular dermatology insights relevant to prevention, early detection, and treatment of basal cell carcinoma (BCC) in high-risk survivors, while anchoring the discussion in a detailed case of multiple BCCs after childhood acute lymphoblastic leukemia and HSCT. (3) Methods: Narrative review integrating clinical, dermoscopic, molecular, and translational data from recent high-impact studies; case retained in full. (4) Results: Radiation exposure (especially total body irradiation), prior immunosuppression, and persistent immune dysregulation synergize with ultraviolet mutagenesis to create a “field cancerization” state characterized by Hedgehog-pathway activation (Patched1/Smoothened), impaired Deoxyribonucleic Acid damage response, and stromal remodeling. Dermoscopy, when embedded in routine whole-body examinations, markedly improves accuracy for keratinocyte cancers. Chemoprevention (e.g., nicotinamide) and targeted therapies (hedgehog inhibitors; Programmed Death-1 blockade) represent key translational levers for care innovation. (5) Conclusions: Integrating structured dermatologic surveillance with molecularly informed prevention and therapy should be standard in survivorship pathways for hematopoietic stem cell transplantation/Radiotherapy-exposed patients. Full article

Background: Posaconazole is an antifungal medication used to treat invasive fungal infections (IFI) in pediatric onco-hematological patients. Its approval for pediatric use was recent, and limitations still apply. Despite limited data, the safety and efficacy profile appear generally favorable in children. This study describes how posaconazole is used across centers affiliated with the Associazione Italiana Ematologia e Oncologia Pediatrica (AIEOP). Methods: A national survey was conducted among physicians within the AIEOP network to evaluate current use of posaconazole in pediatric cancer patients, including those undergoing hematopoietic stem cell transplantation (HSCT). A 25-item web questionnaire was developed and distributed in June 2024. Data analysis involved descriptive statistics. Results: Twenty-one of thirty-one centers (68%) responded, reporting availability of various posaconazole formulations: oral suspension (76%), delayed-release tablets (95%), and intravenous solution (14%). Posaconazole was primarily used for prophylaxis in patients with acute lymphoblastic leukemia (ALL, 38%), acute myeloid leukemia (AML, 38%), and aplastic anemia (19%). It was also used as secondary prophylaxis against previous possible or probable IFI or as salvage therapy for probable or confirmed aspergillosis or mucormycosis, often combined with other treatments. Drug plasma level monitoring was common but varied in scheduling across centers. Most centers (74%) discontinued posaconazole if adverse events suspected drug–drug interactions, such as with vincristine. Conclusions: Posaconazole is widely used in AIEOP centers, though application varies significantly. This variability emphasizes the need for prospective studies to better define indications, dosing, and monitoring protocols for pediatric use of this antifungal. Full article

Background: Pediatric non-Down Syndrome Acute Megakaryoblastic Leukemia (non-DS-AMKL) is a rare subtype of Acute Myeloid Leukemia (AML) arising from primitive megakaryocytes and is associated with poor outcomes. Given its high incidence of relapse, this subpopulation of children is frequently referred for allogeneic hematopoietic stem cell transplant (allo-HSCT) in first complete remission (CR1). Objectives: The objective of this study was to describe the clinical outcomes of non-DS-AMKL pediatric patients in a large, single-institution cohort. Methods: A retrospective review of the medical records of thirty-six patients diagnosed with non-DS-AMKL treated at Texas Children’s Hospital from 2000 to 2022 was conducted. Results: Twenty-nine patients were included in the analysis, with cohorts defined by intention to treat. Twelve patients received chemotherapy only during upfront therapy, and seventeen received upfront HSCT. The 5-year overall survival (OS) and disease-free survival (DFS) for the entire cohort were 19.1% and 24.1%, respectively, with a median survival of 17.4 months. A higher percentage of patients in the chemotherapy-only group had relapsed/refractory disease at death (chemotherapy only, n = 9; HSCT, n = 8). However, 5-year OS and DFS were similar for both groups (OS = 18.8% vs. 31.3%, p = 0.58; DFS = 37.6% vs. 22.2%, p = 0.51). Relapse was the leading cause of death (5-year cumulative incidence of relapse (CIR) 0.78). Treatment with allo-HSCT did not improve outcomes due to the high CIR, even after HSCT in CR1. Conclusions: These dismal outcomes highlight the need for development and incorporation of novel targeted agents into upfront therapy or in the post-HSCT setting for patients with this challenging disease. Full article

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy, typically presenting with systemic symptoms and mediastinal involvement. Leukemia cutis (LC) and renal infiltration are rare, especially at disease onset. A 27-year-old man presented with a solitary scalp lesion without systemic symptoms or hematologic abnormalities. Histopathology revealed a blastoid lymphoid infiltrate with a T-ALL immunophenotype. Two weeks later, laboratory tests showed leukocytosis, lymphocytosis, and renal dysfunction. Imaging revealed a large mediastinal mass, scalp soft tissue involvement, and bilateral renal infiltration. Bone marrow biopsy confirmed T-ALL with a mature phenotype. FISH identified TRAD:NKX2 rearrangement and CDKN2AB deletion. The patient received three cycles of pediatric-inspired chemotherapy, achieving complete molecular remission and resolution of extramedullary disease. He subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-matched sibling. Post-transplant complications included febrile neutropenia and mucositis. On day +100, he remained in minimal residual disease (MRD)-negative remission. This case illustrates a rare presentation of T-ALL with isolated skin involvement and renal infiltration at diagnosis, highlighting the importance of early biopsy and immunophenotyping of atypical skin lesions. Intensive chemotherapy followed by HSCT represents a viable strategy for young adults with high-risk T-ALL and extramedullary disease. Full article

Background/Objectives: Busulfan is a key component of myeloablative conditioning regimens in hematopoietic stem cell transplantation (HSCT) for pediatric patients with acute myeloid leukemia, solid tumors, and certain non-malignant diseases. This study compares the clinical outcomes of once-daily (BU1) versus four-times-daily (BU4) busulfan dosing regimens in pediatric HSCT recipients. Methods: A retrospective analysis was conducted on 70 pediatric patients who underwent HSCT at Hadassah Medical Center between June 2018 and October 2023. Thirty-five patients received the BU4 regimen, and 35 received BU1. The primary endpoint was 100-day event-free survival (EFS). Results: There was no statistically significant difference in 100-day event-free survival between the BU1 group (88.6%) and the BU4 group (85.7%; p = 0.768). Similarly, no significant differences were found in time to neutrophil engraftment (p = 0.251) or platelet engraftment (p = 0.688). Sinusoidal obstruction syndrome (SOS) occurred in 17.1% of patients in each group. No significant differences were observed in the increase in liver enzyme levels (p = 1.0). The incidence of acute graft-versus-host disease was comparable between the groups (41.9% for BU1 vs. 40.0% for BU4; p = 0.878). Conclusions: Once-daily and four-times-daily busulfan regimens demonstrated comparable clinical outcomes in terms of efficacy and adverse events. Further prospective studies are needed to validate these findings. Full article

Background and Clinical Significance: Acute megakaryoblastic leukemia (AMKL) is a rare and aggressive hematologic malignancy. The presence of genetic abnormalities often increases the complexity of AMKL. Among these, patients with monosomy 7 constitute a high-risk group associated with a poorer prognosis and greater chemoresistance. We report the case of a 10-year-old boy who had AMKL along with monosomy 7 and familial GATA2 deficiency. The case highlights the diagnostic and therapeutic challenges faced, as well as the critical importance of early genetic screening and timely hematopoietic stem cell transplantation (HSCT). Case Presentation: A 10-year-old boy presented with easy bruising and pancytopenia. AMKL was diagnosed with the help of a bone marrow biopsy and immunophenotyping. Genetic testing showed a GATA2 mutation and monosomy 7. Two induction cycles with daunorubicin and cytarabine were administered but failed to eliminate residual disease. The patient also developed pneumonia of a fungal origin. HSCT was delayed due to liver toxicity and elevated minimal residual disease (MRD). Azacitidine and venetoclax stabilized the disease, thereby allowing for successful haploidentical HSCT. The patient achieved complete remission with full donor chimerism. Conclusions: This case emphasizes the importance of early molecular diagnostics in pediatric AMKL. Identifying GATA2 mutations and monosomy 7 early can help guide risk stratification and the timing of HSCT. Multimodal therapy, which includes the use of infection control and targeted agents, is important for improving the outcomes in high-risk patients. Full article

Background/Objectives: The aim of this study is to describe fertility preservation (FP) techniques performed over the last 10 years at a tertiary hospital in northern Spain in patients under 18 diagnosed with cancer. Methods: A retrospective medical record review was conducted for patients aged 0 to 18 years diagnosed between January 2014 and December 2023 in the Pediatric Oncology Unit at a university hospital. We evaluated patient characteristics, the timing of FP procedures, and potential risk factors for ovarian insufficiency and early azoospermia. Additionally, we assessed the agreement between two gonadotoxicity risk classifications. Results: In our center, FP is more frequently offered to pubertal patients (12 to 16 years old), prior to treatment in those at high risk of subsequent gonadotoxicity (>80%), and after treatment in those at low risk (<20%). Additionally, the increased provision of FP over the last five years of the study suggests improved clinician uptake of this long-term effect of cancer treatment. Our study found weak agreement between available gonadotoxicity risk classifications, complicating the identification of FP candidates. Long-term follow-up of survivors allowed for the detection of ovarian insufficiency (1.2%) and early azoospermia (0.7%), enabling hormone replacement therapy when necessary. Hematopoietic stem cell transplantation (HSCT) emerged as a predictor of early infertility. Conclusions: Our study highlights the prevalence of gonadotoxicity in pediatric cancer patients at our center and the increasing access to FP techniques. The findings emphasize the importance of personalized medicine, tailored FP strategies based on individual risk, and long-term follow-up to assess fertility status. Full article

Background/Objectives: Pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT) is complicated by iron overload and hypomagnesemia, both contributing to immune dysfunction and post-transplant morbidity. The combined impact of these metabolic disturbances on pediatric allo-HSCT outcomes remains unexplored. This study aims to determine whether hypomagnesemia can serve as a prognostic biomarker for delayed immune reconstitution and explores its interplay with iron overload in predicting post-transplant complications and survival outcomes. Methods: A retrospective analysis was conducted on 163 pediatric allo-HSCT recipients. Serum magnesium levels were measured at defined intervals post-transplant, and outcomes were correlated with CD4+ T cell recovery, time to engraftment, incidence of graft-versus-host disease (GVHD), and survival within 12 months. Iron status, including siderosis severity, was evaluated using imaging and laboratory parameters obtained from clinical records. Results: Patients who died within 12 months post-transplant exhibited significantly lower magnesium levels. Hypomagnesemia was associated with delayed CD4+ T cell recovery, prolonged engraftment, and an increased risk of acute GVHD. A strong inverse correlation was observed between magnesium levels and the severity of siderosis. Iron overload appeared to exacerbate magnesium deficiency. Additionally, the coexistence of hypomagnesemia and siderosis significantly increased the risk of immune dysfunction and early mortality. No significant association was found with chronic GVHD. Conclusions: Hypomagnesemia is a significant, early predictor of poor outcomes in pediatric allo-HSCT, particularly in the context of iron overload, underscoring the need for early intervention, including iron chelation and MRI, to improve outcomes. Full article

Background: Acinetobacter, specifically A. baumannii, are becoming a great threat to hospitalized patients due to increasing antibiotic resistance. The aim of this study was to describe the epidemiology, clinical characteristics, antimicrobial susceptibility pattern and outcome of Acinetobacter infections in pediatric cancer patients and hematopoietic stem cell transplant (HSCT) recipients in Poland. Methods: A total of 125 episodes of Acinetobacter species infections were reported in patients <18 years treated in Polish pediatric hematology and oncology centers over a period from 2012 to 2023. Infections were subdivided into oncohematological disease (OHD) group (n = 106; 84.8%) and HSCT group (n = 19; 15.2%). Each episode represented a separate infection event; therefore, a patient who was infected more than once during the course of treatment was counted for each infection episode. Results: A. baumannii is the most common Acinetobacter species in all groups. The most common diagnoses in OHD group were acute lymphoblastic leukemia (ALL) (n = 32; 30.2%) and acute myeloid leukemia (AML) (n = 13; 12.3%). The most common underlying diseases that were indication for HSCT were hemophagocytic lymphohistiocytosis (n = 3; 15.8%) and neuroblastoma (n = 3; 15.8%). Mortality was significantly higher in the HSCT group compared to the OHD group. In the OHD group, deaths did not correlate with the type of antibiotic, with an exception for gentamicin, which correlated with higher mortality. In the HSCT group, deaths did not correlate with the type of antibiotic, except for levofloxacin that was correlated with a higher mortality rate. Conclusions: Acinetobacter infections are a great danger to immunocompromised patients. More research is needed in order to prevent and treat antibiotic-resistant bacteria. Full article

Graft-versus-host disease (GVHD) remains a significant barrier to the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT), contributing to long-term morbidity and non-relapse mortality in both pediatric and adult populations. Central to GVHD pathophysiology is the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, where JAK2 mediates key pro-inflammatory cytokines, including IL-6, IFN-γ, and GM-CSF. These cytokines promote donor T cell activation, effector differentiation, and target organ damage. The introduction of ruxolitinib, a selective JAK1/2 inhibitor, has transformed the treatment landscape for steroid-refractory acute and chronic GVHD, leading to improved response rates and durable symptom control. However, its limitations—such as cytopenias, infectious complications, and incomplete responses—have catalyzed the development of next-generation agents. In 2024, the FDA approved axatilimab, a CSF-1R inhibitor that targets monocyte-derived macrophages in fibrotic chronic GVHD, and remestemcel-L, an allogeneic mesenchymal stromal cell therapy, for pediatric steroid-refractory acute GVHD. Both agents offer mechanistically distinct and clinically meaningful additions to the therapeutic armamentarium. In parallel, emerging combination strategies involving JAK2 inhibitors and novel biologics show promise in enhancing immune tolerance while preserving graft-versus-leukemia (GvL) effects. Recent advances in biomarker development, such as the MAGIC Algorithm Probability (MAP), are enabling early risk stratification and response prediction. The integration of these tools with organ-specific and personalized approaches marks a shift toward more precise, durable, and tolerable GVHD therapy. This review highlights the current state and future direction of JAK2 inhibition and complementary therapies in the evolving GVHD treatment paradigm. Full article